JAMAICA PLAIN, Mass., May 1 /PRNewswire/ -- Paloma Pharmaceuticals, Inc. today announced it has presented two presentations at the 2008 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) describing the activity of Palomid 529 in a series of models of retinal disease notably macular degeneration, diabetic retinopathy and retinal fibrosis.
P529 is a non-steroidal, synthetic, small molecule drug created through computational design, synthetic and medicinal chemistry, the result of three generations of Palomid design work. Palomid's broad activity as an anti-angiogenic and anti-proliferative agent is shown to reside in its ability to target and inhibit the PI3K/Akt/mTOR signal transduction pathway as a TORC1/TORC2 inhibitor.
The first of the two presentations, "Palomid 529, a Non-Steroidal Small Molecule Anti-Angiogenic Agent Inhibits Retinal and Subretinal Neovascularization by Inhibiting the PI3K/Akt/mTOR Pathway", was given as an oral presentation by Dr. David Sherris, President and CEO of Paloma Pharmaceuticals. The second presentation, "Muller Cell Proliferation and Glial Scar Formation Is Reduced Following Experimental Retinal Detachment Using Palomid 529, an Inhibitor of the Akt/mTOR Pathway", was given by the Drs. Geoffrey P. Lewis and Steven. K. Fisher, presented by Dr. Ethan A. Chapin, of the Neuroscience Research Institute, Neuroscience Research Institute, MCD Biology, University of California-Santa Barbara, Santa Barbara, CA.
"Ocular diseases of both retinal and sub-retinal origin, namely diabetic retinopathy and age-related macular degeneration, are a significant problem in our aging population. In order to create a drug to optimally treat such diseases one needs to prevent or inhibit disease progression caused by the growth of pathological retinal vessels, improve current vision damaged by retinal or sub-retinal blood vessels, inhibit retinal fibrosis and finally formulate for long term drug delivery as these ocular diseases are chronic in nature. We have presented data to support each of these issues in our drug Palomid 529. Palomid 529 is a broad inhibitor of angiogenesis able to inhibit the key pro-angiogenic cytokines (via their synthesis and ability to signal) shown to initiate pathological vessel growth in both age-related macular degeneration and diabetic retinopathy. Our data shows Palomid 529's ability to synergize with anti-VEGF antibody treatment and further to actually allow normal vessel growth to occur while concomitantly inhibiting abnormal vessel growth," says Dr. Sherris.
"A frequent complication of retinal detachment is the induction of cell proliferation, often leading to scar formation that can occur on either surface of the retina. When scars form between the epithelial layer and photoreceptors, termed subretinal fibrosis, regeneration of the photoreceptors is compromised resulting in blindness in that region. When scars occur on the vitreal surface, termed proliferative vitreoretinopathy (PVR), the cells become contractile and cause re-detachment of the retina, again resulting in blindness. We show here using an animal model of retinal detachment that a single intravitreal injection of Palomid 529 dramatically reduces the intraretinal proliferation induced by detachment and subsequently reduces subretinal glial scar formation to a degree not found in any other drugs we have evaluated in our models. These findings suggest that inhibiting the Akt/mTOR pathway by Palomid 529 is a promising new strategy for treating subretinal fibrosis and perhaps the related disease, PVR", says Drs. Lewis and Fisher.
About Angiogenesis and Retinal Vascular Diseases
15 million people in the United States alone have age-related macular degeneration with 2 million new cases each year. About 21 million people in the United State have diabetes. Of those, 15 million are diagnosed and over 6 million are undiagnosed. Of patients who have had type 1 diabetes for more than 20 years, 50% will have proliferative diabetic retinopathy. Between 60- 80% of type 2 diabetes will manifest retinopathy after 15 years, and 20% will progress to proliferative retinopathy after 25 years of duration.
Although it is not entirely clear what initiates pathological retinal vessel formation in either age-related macular degeneration or diabetic retinopathy, it is clear that aberrant retinal vascularization occurs in a manner not unlike that of other pro-angiogenic pathologies such as cancer. Normally, angiogenesis is kept in check by the body naturally creating angiogenic inhibitors to counteract angiogenic factors. However, this balance appears to be offset in the eye by the production of angiogenic growth factors in excess of the angiogenic inhibitors, thus favoring blood vessel growth. Angiogenic factors made by a variety of ocular cell types bind to the normal retinal or subretinal endothelial cell component of their respective vessels, activating it and inducing endothelial signaling events leading to endothelial cell proliferation forming capillaries, moving outward from the retina. The resulting vessels tend to be leaky, structurally aberrant, inefficient and fragile. These aberrant capillaries induce or promote a variety of pathological conditions including acute loss of vision, hemorrhage, rod and cone degeneration, and retinal detachment resulting in scar formation.
About Paloma Pharmaceuticals
Paloma Pharmaceuticals, Inc. is an early stage drug development company focusing on pathologies with a vascular component including cancer, ocular diseases (macular degeneration and diabetic retinopathy), arthritis, fibrotic diseases (pulmonary fibrosis) endometriosis, osteoporosis and skin diseases (psoriasis and atopic dermatitis). Paloma owns the intellectual property relating to a library of novel, proprietary, small molecule drugs created through an integrated design platform incorporating proprietary, customized and industry standard computational tools that has therapeutic potential for the treatment of the foregoing diseases.
CONTACT: David Sherris, [email protected], (617) 407-6314
SOURCE Paloma Pharmaceuticals, Inc.